Quinin esters of aromatic amino acids and process of producing same.



HEINRICH THRON', or mrmmmgoa amn Giannini A'SSIGNOQR .TQ trials FIRM To all whom it may concern or VEREINIGTECHININFABRIKEN, marit me; 001' G. 19;.13. 11,, or FRANxroRT-on-j THE-MAIN, GERMANY.

QUININ ESTERS QR AROMATIC AMIN'o AomsfAN rRocEss or'irnonuome SAME. f i

No Drawing.

Be it known that I, HnINRIoIi THnoN, a subject of the German dent of Frankfort-on-the-Main, Germany,

have invented certain new and useful Improvements in Quinin Esters of Aromatic Amino Acids and Same, of which the following is a specification. a I 1 I I-have succeeded in preparing the hitherto unknown quinin esters of aromatic amino acids which possess very. .i-aluable properties. According to this invention one proceeds most.advantageously in such a manner.

that the qninin ester of the corresponding 'nitro-acid is first prepared (which maybe done in any usual, or suitable, Wayland then the nitro-acidyl-quinin ester isredi ced and so converted into thed'eslred am1no-,

acidyl-ester.

The mannersin which this invention can'be performed, but the invention isnot limited to these examples. The parts are weight.

E wample I .-Pre pcarat-i0 tof" para-aminobenzoyZ-guz'm'n.-Prepare, by the action of para-nitro-benzoyl chlorld on 1 11I11I1, or

- any other usual, or suitable, manner, the

para-nitro'-benzoyl quinin which forms light yellow and tasteless needles, meltsjaij 154 ditficnltly soluble in centigrade, and is very readily soluble ether and cold alcohol, but in hotalcohol and benzene. para-nitro-ben'zoyl quinin' is dissolved in 7 parts of. 10 per cent..hydrochlori'c. acid, mixed with 6 parts of dilutedfalcohol and, after the addition of 4 parts of a percent.

solution of stannons chlorid in per cent. j hydrochloric 3016., the mass is heated for a After coolin short time at boiling point.

the mass is supersaturated with dilute soda lye and shaken with ether. The ethereal solution, after being deprived of alcohol as far as possible by :neans of water and 'concentrated, is allowed to stand and the paraalnino-benzoyl ainin crystallizes in small crystals which arecolorless and tasteless and melt at 17 0 Centigrade. It dissolves readily 1n alcohol, chloroform and hot benzene,

while in ether and petroleum-henzin it is difiicnltly soluble and glves a yellow-brown herapathite. 5

Specificationof Letters Patent;

Emperor, and resi- Processes of Producing following examples illn strat e the fl tens l60.5 centigradev and very "difiicnltly soluble 'in'water, cold alcohol and ether, but readily 1 part of this acid hydrochlorid of the para-aminob'enzoyl-qui'nin which has the composition 9 i i 55 n n 'o coc n un enoi is readily soluble in'water, it is almost tasteless and has therefore a great advantage over the extraordinarily bitter tasting, soluble, neutral and acid salts of quinin, and also over the likewise bitter known-qninin esters.

Example .e-lllqnufectm'e of tlie vorz'fhoi amino-benzoyZ-quiflim-324 parts of quinin (one molecular. proportion) are dissolved in 5,000 "parts ;of henzene, mixed with 185.5 parts of 'orthornitro-benzoyl-chlorid (one molecular proportion) and heated for a few minutes at boiling point. After cooling, extract with dilute hydrochloric acid and shake the "acid, solution with 3,000 parts of ether and ammoniwin excess. The ortho- PatentedMar. 5, 1912;

, Application fi'iea iy a, 191 1. serial 1m. eae',72s.'

soluble salts of the nit i'o-benz oyl'qninin crystallizes almost imlnediately in fine needles, \\-hiclrare subjected to suction and washed with ether and water? f' -lo purify-"it, the'baseis recrystallized from -1 0 parts-of alcohol; it; forms needles melting at from 1(34.5 to

soluble in hot alcoholand chloroform; For the purpose of preparing'the ortho-annnobenzoyl quinin, 1 part of ortho-nitmFbenzoyl qninin, 7 parts of 10 per cent. hydrochloric aci'l; 6 parts of-d'ilnted alcohol, and -l partsof a 00 per cent. solution of stannous chlori'cl" 111 25 per cent. of hydrochlor c- -tl(ld. are

heated'foran hour to the boiling poiut..-

\Vhile still lukci'rarm. the" mass shaken with 14 parts of '20 per cent. soda-lye and 10 parts of ether until almost the whole is dissolved. The ethereal solution is separated, washed with water and dried. On standing, the ortho-amino-henzoyl quinin crystallizes in thick octahedrons which are tasteless and colorless and meltiat from to 137;? centigrade. The) are, readily soluble in alcohol and chloroform. but are diilicultly -solub le 'in other and p0.roleom-lwnzin. The

acid lrvdrochlorid ofthis body which has the composition .is a yellow powder readily soluble in water,

which powder is almost tasteless and has an anesthetic action.

Example IH.-il[anufacture of the 5- a-mz'm-saZ-icyl-quininr-324 parts of quinin (one molecular proportion) and '259 parts of 5-nitro-salol are heated in a vacuum for 4: hours at atemperature (if from 140 to 145 centigrade. the phenol distilling ofi. The residue is heated with benzene and yellow small 'lamellar crystals containing benzene are obtained which, after being .recrystallized from benzene, melt at 112 centigrade. On being boiled with '12 parts of 5 per cent. sulfuric acid, they dissolve and when the solution cools, the acid sulfate of 5-nitro-salicyl-quinin crystallizes out inyellow, tasteless leaflets which are very diliicultl soluble in cold water and alcohol, but a readily soluble in hot alcohol.

In order to prepare the 5-amino-salicyl quinin, 1 part of acid sulfatecf'S-nitrosalicyl-quinln, 5 parts of 10 per cent. hydrochloricvacid, 4 parts ofdiluted alcohol and 3,parts of 60 per cent. solution of stannous chlorid are heated for half an hour on the waterbath. lVhen the mass has cooled, it is sliaken with arts of 10 per cent. soda lye and 15- parts of ether; the alkaline solution is separated from the ethereal solution of the 3d 5 -'aminosalicyl quinin, which latter is washed with water and sh'alten with 1.2 parts of 10 per cent. hydrochloric acid. On evaporating. the hydrochlorid solution, the acid hydrochlorid of 5-amino-salicyl-quinin which has the composition isobtained as a red-yellow powder readily soluble in water and alcohol and having scarcely any bitter taste.

The quinin esters of other aromatic amino acids can be prepared in an analogous manner.

I claim:

1. The herein described process of producing quinin esters of aromatic amino acids which comprises reducing the quinin esters of the corresponding aromatic'nitro-acids.

2. The herein described process of producing quinin esters of aromatic amino acids which comprises reacting on quimn with an acidylizing reagent containing the nitro acidyl radical of an aromatic nitro-carboxylic acid, and reducing the thus obtained nitro-acidyl-quinin.

3. The herein described process of producing amino-benzoyl-quinins which comprises reducing the corresponding nitro-benzoylqunnns. a a

4:. The herein described process of producing amino-benzoyl-quinins which comprises reacting on quinin with a nitro-benzoylchlorid, and reducing the nitro-benzoylquinin thus obtained. i 5. The herein described process of producing para-alnino-benzoyl-quinin which comprises reacting on quinin with para-nitrobenzoyl chlorid, and reducing the paranitro-benzoyl-quinin thus obtained.

6. The herein described qu inin esters of aromatic amino acids of the following gen eral formula C. H N O. ..X where X represents the amino-acidyl radical of an aromatic amino acid, said products forming colorless and tasteless crystals, readily soluble in alcohol, and forming acid hydrochlorids readily soluble in water, substantially as described.

7. The herein described amino benzoylquinins, forming colorless and tasteless crystals readily soluble in alcohol, and forming water soluble acid hydrochlorids having the following formula:

o n n o oo.o mnn enol.

S. The herein described para-amino-bem' zoyl-quinin, forming colorless and tasteless crystals melting at 170 G., being readily soluble in alcohol, chloroform and hot benzene, and forniing a water soluble acid hydrochlorid.

In testimony whereof I have signed my name to this specification in the presence of two subscribing witnesses.

' HEINRICH THRON.

Witnesses J Ii-AN- Gmmn, CARL GRUND. 

